Effect of maternal thyroparathyroidectomy before gestation on fetal development in rats.

Female rats were thyroparathyroidectomized (TPTX) at 24 (immature), 40 (pubertal) and 75 (matured) days of age, at least 21 days before mating. Thyroxine (2.5 microgram/kg) or parathyroid hormone (150 USP units/kg x 2) was replaced in two TPTX groups. Thyroxine deficient groups of all ages had reduced body weight, litter size and serum thyroxine and calcium level. Fetal weights at 20 days of gestation in all thyroxine deficient groups were significantly reduced but placental weight was generally increased. Maternal serum thyroxine and fetal weight was positively related when all groups were taken together, but maternal serum calcium and fetal weight was not related. There were no significant differences in gross, visceral or skeletal anomalies in the fetuses in any group.     

Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats

Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.     

Effect of estrus cycle, ovariectomy and lactation on variations of basal corticosterone levels or agression stress levels in rats]

In the Rat, the estrous cycle induces a rhythm of plasmatic corticosterone level : the fluctuations of basal or stress corticosteronemy are significantly superior during the periods of high estradiol secretion, proestrus and estrus, that during metaestrus and diestrus. Ovariectomy, performed at 60 days of age, is without effect on resting corticosteronemy, but reduces significantly the response to stress. Weaning unaffects the basal level of plasmatic corticosterone which remains comparable to diestrus level ; however, stress response decreased during lactation returns to normal level at the end of the first ovarian cycle (diestrus).     

Bone loss induced by ovariectomy in rats is prevented by gene transfer of parathyroid hormone or an Arg-Gly-Asp-containing peptide

Osteoporosis is a major and growing healthcare concern as the population ages. The genes of both a Arg-Gly-Asp (RGD)-containing peptide and parathyroid hormone (PTH) were used to reduce bone loss induced by ovariectomy (OVX) in rats. Plasmids with either RGD or PTH gene were delivered into the quadriceps of OVX rats. The expression of the genes was detected by RT-PCR and radioimmunoassay. Analysis of bone mineral density, bone mechanical testing and bone mineral content indicated an improvement in bone properties in both RGD-transferred and PTH-transferred rats compared to OVX rats. Gene transfer of either RGD or PTH is therefore a possible approach to prevent bone loss in OVX rats thus providing a potential method to prevent osteoporosis in clinical situations.These authors contributed equally to this work     

Effect of predator-induced maternal stress during gestation on growth in root volesMicrotus oeconomus

We studied the effect of maternal stress evoked by a severe stressor from the cues of predation risk during gestation on the growth of offspring in root volesMicrotus oeconomus Pallas, 1776. Body mass of both male and female offspring was significantly reduced in the period from birth to weaning. Females showed compensatory growth after weaning, whereas males maintained low body mass at weaning into adulthood. Maternal stress led to an elevated plasma corticosterone level in male offspring, but did not affect that of female offspring. Corticosterone levels remained elevated in males from stressed dams into adulthood. Increased levels of plasma corticosterone may have led to the inhibition of pituitary growth hormone and a chronically abnormal energy mobilization, considering the greater energy and metabolic requirements of male offspring, this may account for the sex-specific differences in compensatory growth. We suggest that in the high stress situation, endocrine-based sex-biased effects of maternal stress as a primary factor can lead to long-term physical and ecological consequences for male offspring.     

Developmental alternations in offspring of female rats orally intoxicated by aluminum chloride or lactate during gestation

The oral treatment of pregnant rats by aluminum chloride or lactate at various doses was applied from day 1 to day 21 of gestation to determine its influence on mortality, weight evolution, and neuromotor maturation of their pups. No effect of treatment on litter size was detected, but an increased mortality appeared during the first week: treatment by aluminum lactate was less active than was an equivalent treatment by aluminum chloride. Weight was transitorily delayed, but the reversal of this effect could be attributed to the decrease of litter size. The neuromotor maturation of surviving pups treated with the two aluminum salts showed an important impairment during the first 2 weeks of postnatal life.     

紫杉醇加铂类和环磷酰胺加铂类方案对卵巢上皮性癌疗效

目的:探讨紫杉醇加铂类(PT组)和环磷酰胺加铂类(PC组)在卵巢上皮性癌初治患者中的疗效.方法:时1998年1月至2004年1月第四军医大学西京医院和第三军医大学大坪医院收治的78例卵巢上皮性癌术后患者进行回顾性分析,其中PT组36例.PC组42例,比较两组的近期疗效和3年存活率、无进展生存时间以及不良反应.结果:PT和PC方案的患者化疗有效率分别为77.8%和66.7%(P＜0.01),中位生存时间分别为29个月和23个月(P＜0.01),中位无进展生存时间分别为23个月和15个月(P＜0.01),3年存活率分别为41.7%和19.0%(P＜0.05).在早期(Ⅰ期+Ⅱ期)卵巢癌患者中,PT组和PC组中位生存时间和中位无进展生存时间差异无统计学意义,但中晚期(Ⅲ期+Ⅳ期)患者PT组和PC组中位生存时间和中位无进展生存时间分别为25.4月和21.0月以及16.1月和7.9月(P＜0.05),有统计学意义,表明PT方案对中晚期患者可能更具有优势.PT组脱发和血液学毒性发生率高于PC组,而消化系统毒性和肝肾功损害发生率低于PC组.结论:卵巢癌的辅助化疗中,PT方案在化疗反应率、无进展生存时间及3年存活率均优于PC方案,对中晚期患者,前者的优势更为显著.     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

Juvenile hormone in earwigs: Roles in oogenesis,mating, and maternal behaviors

The role of juvenile hormone (JH) in courtship, mating, maternal behavior, and the ovarian cycle was studied in the ring-legged earwig, Euborellia annulipes (Lucas). The single, median corpus allatum makes and secretes JH III. JH III production was low in newly eclosed adult females, increasing as oocytes developed, maximal at about the time of oviposition, and low again in brooding females. Application of 35 or 122 μg JH III to newly eclosed females hastened the onset of courtship behavior, but had no effect on the age at which females first mated nor on the duration of mating, though the trend is toward advanced onset. Hormone treatment advanced the age of first oviposition and reduced clutch size and the proportion of eggs hatching but did not affect the interval from oviposition of the first clutch to oviposition of the second clutch, nor the size and proportion hatching of the second clutch. Acetone treatment and treatment with 6 μg JH III did not affect these parameters. Application of 50 μg JH III to females on the day of oviposition shortened the duration of maternal care and advanced the onset of the second gonadotropic cycle, compared with that of acetone-treated and precocene II-treated females. The duration of maternal care was positively correlated with the proportion of eggs hatching. JH titer analysis confirmed JH III to be the predominant hormone in this species and clearly demonstrated the absence of other homologues. This work also confirmed our hypothesis that intermediate to high levels of JH are associated with oocyte growth, mating, and cessation of maternal care; low levels of JH are associated with the period of maternal behavior and slow ovarian development. We are currently investigating factors which might regulate corpus allatum activity during the reproductive cycle and the subsequent period of maternal care. Arch. Insect Biochem. Physiol. 35:427–442, 1997. © 1997 Wiley-Liss, Inc.     

Effect of long-term restriction of protein intake,from gestation onward,on free-choice consumption of ethanol by rats

Long-term (including gestational and lactational) restriction of protein (8% of diet) significantly lowered the absolute and relative consumption of 6% ethanol (EtOH) in a two-bottle, free-choice (H₂O vs EtOH) situation during a 76-day test period. This difference in response between rats fed the low protein diet and those fed an isocaloric normal protein (24%) diet became non-significant in two subsequent 100-day test periods. Statistical analysis of observations on individual performance indicated that regularity, cyclicity, and duration of drinking in each animal was random over all three time intervals for both groups. The early, significantly lower EtOH consumption by the protein-restricted group may be due to a paucity of EtOH-metabolizing enzymes in brain and liver, thereby prolonging the CNS effects of lower doses of EtOH consumed. The disappearance of this difference in subsequent test periods may reflect either a behavioral or metabolic adaptation in the developing protein-deficient rat.     

Effect of mastectomy versus mastectomy plus adjuvant ovariectomy on prolactin response to TRH in breast cancer

The endocrine effects of ovariectomy need to be further investigated. The present study was carried out to evaluate the influence of the adjuvant ovariectomy on the mastectomy-induced changes in PRL response to TRH in breast cancer. The study included 34 patients with locally limited breast carcinoma, 18 of whom were treated with radical mastectomy, whereas the other 16 underwent mastectomy plus adjuvant ovariectomy. PRL secretion in response to TRH (200 mcg I.V. as bolus) was evaluated one day before and 7 days after surgery. In patients treated with mastectomy only, PRL increase after TRH was significantly higher after surgery than before. On the contrary, no difference was seen in patients treated with mastectomy plus ovariectomy. This study shows that the adjuvant ovariectomy may block the increase in PRL response to TRH induced by mastectomy in breast cancer.     

Effect of maternal chronic hypoxic exposure during gestation on apoptosis in fetal rat heart

Chronic hypoxia during pregnancy is one of the most common insults to fetal development. We tested the hypothesis that maternal hypoxia induced apoptosis in the hearts of near-term fetal rats. Pregnant rats were divided into two groups, normoxic control and continuous hypoxic exposure (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from fetal rats of 21-day gestational age. Maternal hypoxia increased hypoxia-inducible factor-1alpha protein in fetal hearts. Chronic hypoxia significantly increased the percentage and size of binucleated myocytes and increased apoptotic cells from 1.4 +/- 0.14% to 2.7 +/- 0.3% in the fetal heart. In addition, the active cleaved form of caspase 3 was significantly increased in the hypoxic heart, which was associated with an increase in caspase 3 activity. There was a significant increase in Fas protein levels in the hypoxic heart. Chronic hypoxia did not change Bax protein levels but significantly decreased Bcl-2 proteins. In addition, chronic hypoxia significantly suppressed expression of heat shock protein 70. However, chronic hypoxia significantly increased expression of the anti-apoptotic protein 14-3-3, among other 14-3-3 isoforms. Chronic hypoxia differentially regulated beta-adrenoreceptor (beta-AR) subtypes with an increase in beta1-AR levels but no changes in beta2-AR. The results demonstrate that maternal hypoxia increases apoptosis in fetal rat heart, which may be mediated by an increase in Fas and a decrease in Bcl-2 proteins. Chronic hypoxia-mediated increase in beta1-AR and decrease in heat shock proteins may also play an important role in apoptosis in the fetal heart.     

Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in foetal rats by maternal cholestyramine feeding

Late gestation foetus from rats fed a non-absorbable bile acid binding resin (cholestyramine) have increased hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. This was due to increased unphosphorylated (active) as well as total reductase and was accompanied by higher fatty acid synthetase activity. No increase in foetal hepatic cystathionase or tyrosine aminotransferase activity, or changes in plasma insulin, corticosterone or thyroxine were found. The studies demonstrate that foetal hepatic cholesterol metabolism is sensitive to drug-induced perturbation of maternal lipoprotein metabolism. The data suggest induction of foetal cholesterol and fatty acid synthesis by a specific mechanism not involving generalized hormone-induction of hepatic enzyme systems. Cholestyramine appears to have application for in vivo study of the regulation of foetal cholesterologenesis and its coordination to maternal and foetal steroid requirements.     

Hormonal regulation of maternal behavior in rats: stimulation following treatment with ectopic pituitary grafts plus progesterone

Changes in hormone secretions during pregnancy help to stimulate the onset of maternal behavior at parturition. To date, studies have demonstrated that estradiol (E2) appears to be a necessary component in the hormonal induction of maternal behavior in rats and other mammals. In the present study, we have reevaluated the contribution of E2, progesterone (P), and hormone-secreting pituitary grafts in the rapid induction of maternal behavior by measuring the behavioral effects of exposure to various combinations of P and prolactin-secreting ectopic pituitary grafts in the absence of estrogen. Adult hypophysectomized and nonhypophysectomized nulliparous rats were ovariectomized 2-3 days (Treatment Day 1) after their arrival in our laboratory. In Experiment #1, experimental, hypophysectomized rats were implanted s.c. with 6 P-filled Silastic capsules and given 2 anterior pituitary (AP) glands that were grafted beneath the kidney capsule on Treatment Day 1. Controls were given blank implants and were sham-grafted. P-filled and blank Silastic capsules were removed on Day 11, and behavioral testing was conducted once-a-day beginning on Day 12 for eleven days. Animals treated with P-plus-pituitary grafts displayed full maternal behavior significantly faster than did controls (median latencies of 3.0 and 7.5 days, respectively). In Experiment #2, nonhypophysectomized rats were assigned to one of three treatments. On Treatment Day 1, one group of rats received 6 P-filled Silastic implants and had 2 AP glands grafted under their renal capsules. A second group of animals received 6 P capsules and was sham-grafted, while controls were given blank implants and were sham-grafted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proliferative growth of neonatal cerebellar cells in culture: Regulation by male and by maternal serum in late gestation

Neonatal cerebellar cells were utilized as a model system to examine the effect of 20 day pregnant rat serum on proliferative growth in the CNS. Cells were prepared by mechanical dissociation and cultured as mixed cells or populations enriched in astrocytes or oligodendrocytes. Cell proliferation was estimated by measurement of DNA, protein, and/or mitochondrial reductase activity (MTT). When mixed cells were incubated with 10% male rat serum, both total DNA and protein content increased after 6 days of culture. By contrast, neither of these parameters were altered in cultures incubated with 10% pregnant serum. When cells were incubated with either male or pregnant sera, changes in MTT activity paralleled changes in protein content. Graded concentrations of pregnant serum (5–20%) added to mixed cell cultures produced consistently lower MTT values when compared with identical concentrations of male serum. In addition, MTT activity was diminished in both astrocytes and oligodendrocytes incubated with graded concentrations of pregnant sera when compared with similar concentrations of non-pregnant sera. When potential effects of these different sera on the cell cycle were examined, an increase in the number of cells in the S and G2/M phase was similar, and DNA doubling began to increase at 96 hrs in the presence of either male or 20 day pregnant sera. Thus the inhibition of cell growth by pregnant serum was not likely a result of either cytotoxicity or a delay of entry of cells into the cell cycle. To examine whether this inhibition of cell growth may reflect the effect of pregnant serum on endogenous growth factor production, we tested the production of IGF-II by cerebellar cells. Production of an endogenous source of IGF-II was apparent using an RNAse protection assay and was noted using Slot Blot analysis of mRNA extracted at sequential times during cell incubation. Mixed cell cultures also secreted immunologically defined IGF-II. These observations are consistent with the previous demonstration that the fraction of pregnant serum which bound IGF-II also inhibited cell growth. The inhibitory effect of pregnant serum was diminished by preincubating aliquots of sera with graded concentrations of IGF-I prior to adding sera to tissue culture medium. Pregnant serum inhibition was also diminished by prolonging incubation times beyond 6 days. The blunting of pregnant serum inhibition may have been consequent to either a continuing production of endogenous growth factors or to the potential emergence of resistant cells due to prolonged tissue culture incubation. Since cells studied in a primary culture of limited duration may more accurately reflect the physiologic properties of this tissue, the model presented herein could provide a new approach to study brain development.West Side Medical CenterNorthwestern University medical School     

Effect of prolonged glucose infusion into fetal sheep on body growth, fat deposition and gestation length

Eleven Merino sheep fetuses were supplemented with glucose by direct continuous intravenous infusion of 50% dextrose into the fetus from day 115 of gestation until spontaneous delivery. Infusion rates of 15 or 25 g/day per kg were used and equivalent volumes of saline were infused into 11 control fetuses. Infusion periods approximated 27 days in both groups. Fetal plasma glucose concentrations were significantly (P less than 0.001) elevated throughout glucose infusion and resulted in variable but consistently higher plasma insulin concentrations in the glucose than in the saline-infused fetuses. Glucose-infused fetuses were significantly heavier than controls (mean +/- SEM; 3.86 +/- 0.16 vs 3.28 +/- 0.24 kg, P less than 0.05) and body fat depots (in g/kg body wt.) were larger in glucose-infused than control fetuses (9.91 +/- 0.65 vs 6.73 +/- 0.37, P less than 0.005, for internal brown fat depots; 1.25 +/- 0.44 vs 0.27 + 0.13, P less than 0.05, for subcutaneous white adipose tissue). The results indicate that growth and lipid deposition in the sheep fetus are responsive to increased glucose supply, an effect which may be mediated through the actions of insulin. Mean gestation length was 146.60 +/- 1.45 days for controls and 144.18 +/- 1.23 days for glucose-infused animals (normal term 150 days).     

Induction by perfluorinated fatty acids with different carbon chain length of peroxisomal beta-oxidation in the liver of rats

The potency of the induction of peroxisomal beta-oxidation was compared between perfluorinated fatty acids (PFCAs) with different carbon chain lengths in the liver of male and female rats. In male rats, perfluoroheptanoic acid (PFHA) has little effect, although perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) potentially induced the activity. By contrast, PFHA and PFOA did not induce the activity of peroxisomal beta-oxidation in the liver of female rats while PFNA and PFDA effectively induced the activity. The induction of the activity by these PFCAs was in a dose-dependent manner, and there is a highly significant correlation between the induction and hepatic concentrations of PFCAs in the liver regardless of their carbon chain lengths. These results strongly suggest that the difference in their chemical structure is not the cause of the difference in the potency of the induction. Hepatic concentrations of PFOA and PFNA was markedly higher in male compared with female rats. Castration of male rats reduced the concentration of PFNA in the liver and treatment with testosterone entirely restored the reduction. In contrast to the results obtained from the in vivo experiments, the activity of peroxisomal beta-oxidation was induced by PFDA and PFOA to the same extent in cultured hepatocytes prepared from both male and female rats. These results, taken together, indicate that difference in accumulation between PFCAs in the liver was responsible for the different potency of the induction of peroxisomal beta-oxidation between PFCAs with different carbon chain lengths and between sexes.